Evidence map›Paper›PMID 34071840›Full record

ArticlePharmaceutics2021

PEGylation of mRNA by Hybridization of Complementary PEG-RNA Oligonucleotides Stabilizes mRNA without Using Cationic Materials.

Naoto Yoshinaga, Mitsuru Naito, Yoshihiro Tachihara, Eger Boonstra, Kensuke Osada, Horacio Cabral, Satoshi Uchida

Abstract read
In one paragraph

Article in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Nanopore-Based Profiling of PEGylation in Nucleic Acid Therapeutics.Journal of the American Chemical Society · 2026
    Article
  2. Review
  3. In Vivo Interactions of Nucleic Acid Nanostructures With Cells.Advanced materials (Deerfield Beach, Fla.) · 2025
    Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Naoto YoshinagaGraduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.ORCID 0000-0003-4399-0289
Mitsuru NaitoGraduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.ORCID 0000-0002-4237-871X
Yoshihiro TachiharaGraduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Eger BoonstraGraduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.ORCID 0000-0002-5386-7711
Kensuke OsadaNational Institute of Radiological Science, 4-9-1 Anagawa, Inage-ku, Chiba-shi 236-8555, Chiba, Japan.
Horacio CabralGraduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Satoshi UchidaGraduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.ORCID 0000-0001-8726-0478

Funding

Japan Agency for Medical Research and Development JP18ae0201009the Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) 18K03529the Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) 20H04524the Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) JP18K19901
6 · The paper itself

Abstract

Messenger RNA (mRNA) delivery strategies are required to protect biologically fragile mRNA from ribonuclease (RNase) attacks to achieve efficient therapeutic protein expression. To tackle this issue, most mRNA delivery systems have used cationic components, which form electrostatically driven complexes with mRNA and shield encapsulated mRNA strands. However, cationic materials interact with anionic biomacromolecules in physiological environments, which leads to unspecific reactions and toxicities. To circumvent this issue of cation-based approaches, herein, we propose a cation-free delivery strategy by hybridization of PEGylated RNA oligonucleotides with mRNA. The PEG strands on the mRNA sterically and electrostatically shielded the mRNA, improving mRNA nuclease stability 15-fold after serum incubation compared with unhybridized mRNA. Eventually, the PEGylated mRNA induced nearly 20-fold higher efficiency of reporter protein expression than unhybridized mRNA in cultured cells. This study provides a platform to establish a safe and efficient cation-free mRNA delivery system.

Indexed as

mRNA deliverymRNA therapeuticsRNA engineering

Identifiers

PMID34071840
PMCPMC8227728

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.